This is a proposal for a Research Scientist Award that would serve as a renewal/replacement of a Research Scientist Development Award that is expiring after 10 years of support. The applicant serves as director of the Behavioral Pharmacology Research Unit at The Johns Hopkins University School of Medicine. That Unit maintains a large and multifaceted research program on the human behavioral pharmacology of substance abuse and is the site of a NIDA Postdoctoral Research Training Program on that topic. The candidate proposes to continue his directorship of the Research Unit and of the research training program and to pursue clinical research on substance abuse in the following areas: 1) Opioid clinical pharmacology; 2) Clinical pharmacology of other abused drugs (sedatives, benzodiazepines, tobacco, caffeine); 3) Behavioral and pharmacological treatment of drug abuse (opioid, polydrug, cocaine); 4) Cigarette smoking. The aim of the research is to elucidate the determinants and consequences of human drug self-administration and to identify commonalities among and differences between different substance abuse disorders and different types of drug self-administration.